ABSTRACT
STUDY OBJECTIVE: To characterize nephrotoxicity associated with an individualized serum concentration target-specific, once-daily aminoglycoside (ODA) program. DESIGN: Concurrent and retrospective study. SETTING: University-affiliated trauma hospital. PATIENTS: Two hundred patients treated with ODA and 100 treated with individualized traditional dosing (TDA). INTERVENTIONS: Empiric dosing for both groups was based on patient-specific pharmacokinetics and severity of infection. Regimens were modified according to predetermined target maximum and minimum serum concentrations for both groups. MEASUREMENTS AND MAIN RESULTS: Nephrotoxicity occurred in 7.5% patients treated with ODA and 14.7% receiving TDA (p=0.05). Minimum serum concentrations, length of aminoglycoside therapy, and cumulative area under the curve (AUC) were all dependently related to nephrotoxicity, and concomitant vancomycin and other nephrotoxic drugs were independently related to the disorder. The cumulative AUC was greatest in patients receiving TDA (p=0.03), and the modeled probability of becoming toxic at any given cumulative AUC was significantly greater with TDA than with ODA (p<0.01). Clinical and microbiologic outcomes were similar between groups. Maximum concentration:minimum inhibitory concentration ratios were higher (p<0.01) and number of days to organism eradication was shorter in the ODA group (p=0.04). CONCLUSION: The trend was toward decreased nephrotoxicity in patients treated with ODA compared with TDA, and at any given cumulative AUC, the risk of toxicity was lower for ODA.
Subject(s)
Anti-Bacterial Agents/adverse effects , Kidney/drug effects , Aminoglycosides , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Drug Administration Schedule , Humans , Microbial Sensitivity Tests , Retrospective StudiesSubject(s)
Amikacin/chemistry , Anti-Bacterial Agents/chemistry , Gentamicins/chemistry , Tobramycin/chemistry , Amikacin/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Incompatibility , Drug Stability , Gentamicins/pharmacology , Humans , Microbial Sensitivity Tests , Solutions , Syringes , Tobramycin/pharmacologyABSTRACT
The pathogenesis, clinical manifestations, and management of orthostatic hypotension (OH) are reviewed. OH is a decline in blood pressure that occurs when one moves from a lying to a standing position that results in symptoms of cerebral hypoperfusion, most commonly lightheadedness and syncope. The disorder may result from primary autonomic disorders, such as Shy-Drager syndrome; reversible nonautonomic causes, such as reduced blood volume; underlying diseases, such as diabetes mellitus; and drugs. Elderly people are predisposed to OH. The diagnosis of OH is based on the documentation of postural hypotension accompanied by symptoms of cerebral ischemia. The goal of therapy is to relieve symptoms. Nonpharmacologic approaches are preferred and include increasing sodium intake, avoiding rapid postural changes, and wearing elastic garments. OH is difficult to treat pharmacologically because of varying responses and adverse effects. The drug of choice for all types of OH is fludrocortisone acetate, although caution must be used in patients with congestive heart failure. Prostaglandin synthetase inhibitors can also be used for all types of OH but have had more limited success. Sympathomimetics with or without monoamine oxidase inhibitors, beta-adrenergic antagonists, and ergot alkaloids should be administered only to patients with certain types of OH, and patients must be monitored closely. Clonidine, midodrine, yohimbine, octreotide, dopamine antagonists, desmopressin, and epoetin alfa have not been well studied and should be limited to patients with severe, refractory disease. Although no uniformly effective treatment regimen exists, OH can often be adequately managed with a combination of nondrug and drug therapies.
